A study is in progress to determine the effect of diet on the metabolic activity of intestinal microflora and intestinal epithelium. The enzymatic activity of specific reactions which can convert procarcinogens to carcinogens are being studied. The products of these reactions are being measured by standard analytical methods and by a bacterial mutagenic assay. The findings indicate that a high beef diet can alter the enzymatic activity of the intestinal microflora of rats and humans. Higher specific activity is observed for meat-fed-rats, and humans eating a "Western diet" when fecal bacterial nitroreductase, azoreductase, beta-glucuronidase, or steroid-7-dehydroxylase is assayed. A thirty day supplement of bran or elimination of red-meat from the diet for thirty days did not affect these enzymes activities in omnivore subjects. An exception was steroid-7-dehydroxylase activity which decreased approximately two-fold. The addition of Lactobacillus acidophilus supplements to the diet for thirty days did decrease the omnivores' fecal enzyme activities. Fecal extracts when incubated in vitro with nitronaphthalene or nitrofluorene caused a mutagenic response in nitroreductase negative mutants of Salmonella testor strains. The effect of diet on this mutagenic response is now being studied. Animal feeding experiments with naphthylamine and naphthylamine-beta-D-glucuronide indicate the former compound is rapidly absorbed in the upper gastrointestinal tract. The naphthylamine-beta-D-glucuronide does reach the cecum and colon where slow bacterial hydrolysis takes place releasing the naphthylamine. Studies are now underway to detect the rate of this release in the bowel using the Salmonella mutagen assay as an assay system.